1. Swingler, S., Mann, A. M., Zhou, J., Swingler, C. & Stevenson, M. Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein. PLoS Pathog. 3, 1281–1290 (2007).

2. Groot, F., Welsch, S. & Sattentau, Q. J. Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood 111, 4660–4663 (2008).

3. Duncan, C. J. et al. High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse. J. Virol. 88, 2025–2034 (2014).

4. Collins, D. R., Lubow, J., Lukic, Z., Mashiba, M. & Collins, K. L. Vpr promotes macrophage-dependent HIV-1 infection of CD4+ T lymphocytes. PLoS Pathog. 11, e1005054 (2015).

5. Honeycutt, J. B. et al. Macrophages sustain HIV replication in vivo independently of T cells. J. Clin. Invest. 126, 1353–1366 (2016).

6. Honeycutt, J. B. et al. HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. Nat. Med. 23, 638–643 (2017).

7. Avalos, C. R. et al. Quantitation of productively infected monocytes and macrophages of simian immunodeficiency virus-infected macaques. J. Virol. 90, 5643–5656 (2016).

8. Avalos, C. R. et al. Brain Macrophages in simian immunodeficiency virus-infected, antiretroviral-suppressed macaques: a functional latent reservoir. mBio 8, e01186–e01117 (2017).

9. Nowlin, B. T. et al. SIV encephalitis lesions are composed of CD163+ macrophages present in the central nervous system during early SIV infection and SIV-positive macrophages recruited terminally with AIDS. Am. J. Pathol. 185, 1649–1665 (2015).

10. Sattentau, Q. J. & Stevenson, M. Macrophages and HIV-1: an unhealthy constellation. Cell Host Microbe 19, 304–310 (2016).

11. DiNapoli, S. R., Hirsch, V. M. & Brenchley, J. M. Macrophages in progressive human immunodeficiency virus/simian immunodeficiency virus infections. J. Virol. 90, 7596–7606 (2016).

12. Lamers, S. L. et al. HIV-1 Nef in macrophage-mediated disease pathogenesis. Int. Rev. Immunol. 31, 432–450 (2012).

13. Hsu, D. C., Sereti, I. & Ananworanich, J. Serious non-AIDS events: immunopathogenesis and interventional strategies. AIDS Res. Ther. 10, 29 (2013).

14. Streeck, H. & Nixon, D. F. T cell immunity in acute HIV-1 infection. J. Infect. Dis. 202(Suppl 2), S302–S308 (2010).

15. Goulder, P. J. & Walker, B. D. The great escape — AIDS viruses and immune control. Nat. Med. 5, 1233–1235 (1999).

16. Fujiwara, M. & Takiguchi, M. HIV-1-specific CTLs effectively suppress replication of HIV-1 in HIV-1-infected macrophages. Blood 109, 4832–4838 (2007).

17. Severino, M. E. et al. Inhibition of human immunodeficiency virus type 1 replication in primary CD4+ T lymphocytes, monocytes, and dendritic cells by cytotoxic T lymphocytes. J. Virol. 74, 6695–6699 (2000).

18. Walker-Sperling, V. E., Buckheit, R. W. III & Blankson, J. N. Comparative analysis of the capacity of elite suppressor CD4+ and CD8+ T cells to inhibit HIV-1 replication in monocyte-derived macrophages. J. Virol. 88, 9789–9798 (2014).

19. Walker-Sperling, V. E. et al. Short communication: HIV controller T cells effectively inhibit viral replication in alveolar macrophages. AIDS Res. Hum. Retroviruses 32, 1097–1099 (2016).

20. Rainho, J. N. et al. Nef Is dispensable for resistance of simian immunodeficiency virus-infected macrophages to CD8+ T cell killing. J. Virol. 89, 10625–10636 (2015).

21. Vojnov, L. et al. The majority of freshly sorted simian immunodeficiency virus (SIV)-specific CD8. T cells cannot suppress viral replication in SIV-infected macrophages. J. Virol. 86, 4682–4687 (2012).

22. Walker, B. D. & Yu, X. G. Unravelling the mechanisms of durable control of HIV-1. Nat. Rev. Immunol. 13, 487–498 (2013).

23. Slee, E. A., Adrain, C. & Martin, S. J. Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis. J. Biol. Chem. 276, 7320–7326 (2001).

24. Lieberman, J. The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal. Nat. Rev. Immunol. 3, 361–370 (2003).

25. Belizario, J., Vieira-Cordeiro, L. & Enns, S. Necroptotic cell death signaling and execution pathway: lessons from knockout mice. Mediators Inflamm. 2015, 128076 (2015).

26. Lieberman, J. Cell-mediated cytotoxicity. in Fundamental Immunology (ed. Paul, W.E.) 7th edn (Lippincott Williams & Wilkins, Philadelphia, 2013).

27. Kaiserman, D. & Bird, P. I. Control of granzymes by serpins. Cell Death Differ. 17, 586–595 (2010).

28. Kataoka, T. et al. Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity. J. Immunol. 156, 3678–3686 (1996).

29. Sutton, V. R. et al. Granzyme B triggers a prolonged pressure to die in Bcl-2 overexpressing cells, defining a window of opportunity for effective treatment with ABT-737. Cell Death Dis. 3, e344 (2012).

30. Jenkins, M. R. et al. Failed CTL/NK cell killing and cytokine hypersecretion are directly linked through prolonged synapse time. J. Exp. Med. 212, 307–317 (2015).

31. Stepp, S. E. et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science 286, 1957–1959 (1999).

32. Calabia-Linares, C. et al. Endosomal clathrin drives actin accumulation at the immunological synapse. J. Cell Sci. 124, 820–830 (2011).

33. Corbera-Bellalta, M. et al. Blocking interferon γ reduces expression of chemokines CXCL9, CXCL10 and CXCL11 and decreases macrophage infiltration in ex vivo cultured arteries from patients with giant cell arteritis. Ann. Rheum. Dis. 75, 1177–1186 (2016).

34. Foley, J. F. et al. Roles for CXC chemokine ligands 10 and 11 in recruiting CD4+ T cells to HIV-1-infected monocyte-derived macrophages, dendritic cells, and lymph nodes. J. Immunol. 174, 4892–4900 (2005).

35. Reinhart, T. A. et al. Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-? in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome. Blood 99, 3119–3128 (2002).

36. de Poot, S. A. et al. Granzyme M targets topoisomerase II alpha to trigger cell cycle arrest and caspase-dependent apoptosis. Cell Death Differ. 21, 416–426 (2014).

37. Ewen, C. L., Kane, K. P. & Bleackley, R. C. Granzyme H induces cell death primarily via a Bcl-2-sensitive mitochondrial cell death pathway that does not require direct Bid activation. Mol. Immunol. 54, 309–318 (2013).

38. Liu, J. & Roederer, M. Differential susceptibility of leukocyte subsets to cytotoxic T cell killing: implications for HIV immunopathogenesis. Cytometry A 71, 94–104 (2007).

39. Medema, J. P. et al. Expression of the serpin serine protease inhibitor 6 protects dendritic cells from cytotoxic T lymphocyte-induced apoptosis: differential modulation by T helper type 1 and type 2 cells. J. Exp. Med. 194, 657–667 (2001).

40. Migueles, S. A. et al. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat. Immunol. 3, 1061–1068 (2002).

41. Wherry, E. J. T cell exhaustion. Nat. Immunol. 12, 492–499 (2011).

42. Hersperger, A. R. et al. Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control. PLoS Pathog. 6, e1000917 (2010).

43. Trimble, L. A. & Lieberman, J. Circulating CD8 T lymphocytes in human immunodeficiency virus-infected individuals have impaired function and downmodulate CD3 zeta, the signaling chain of the T-cell receptor complex. Blood 91, 585–594 (1998).

44. Draenert, R. et al. Persistent recognition of autologous virus by high-avidity CD8 T cells in chronic, progressive human immunodeficiency virus type 1 infection. J. Virol. 78, 630–641 (2004).

45. Appay, V. et al. HIV-specific CD8+ T cells produce antiviral cytokines but are impaired in cytolytic function. J. Exp. Med. 192, 63–75 (2000).

46. Migueles, S. A. et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity 29, 1009–1021 (2008).

47. Migueles, S. A. et al. Defective human immunodeficiency virus-specific CD8+ T-cell polyfunctionality, proliferation, and cytotoxicity are not restored by antiretroviral therapy. J. Virol. 83, 11876–11889 (2009).

48. Pachlopnik Schmid, J. et al. Neutralization of IFNγ defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice. EMBO Mol. Med. 1, 112–124 (2009).

49. Critchfield, J. W. et al. Magnitude and complexity of rectal mucosa HIV-1-specific CD8+ T-cell responses during chronic infection reflect clinical status. PLoS One 3, e3577 (2008).

50. Pereyra, F. et al. Increased coronary atherosclerosis and immune activation in HIV-1 elite controllers. AIDS 26, 2409–2412 (2012).

51. Pereyra, F. et al. HIV control is mediated in part by CD8+ T-cell targeting of specific epitopes. J. Virol. 88, 12937–12948 (2014).

52. Salerno-Goncalves, R., Fernandez-Vina, M., Lewinsohn, D. M. & Sztein, M. B. Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. J. Immunol. 173, 5852–5862 (2004).

53. Metkar, S. S. et al. Granzyme B activates procaspase-3 which signals a mitochondrial amplification loop for maximal apoptosis. J. Cell Biol. 160, 875–885 (2003).