A role for CD4+ NK1.1+ T lymphocytes as major histocompatibility complex class II independent helper cells in the generation of CD8+ effector function against intracellular infection.
Major histocompatibility complex (MHC) class II (A beta) knockout mice were vaccinated with ts-4, an attenuated mutant strain of Toxoplasma gondii, which in normal animals induces strong T cell immunity mediated by interferon gamma (IFN-gamma). After challenge with the lethal parasite strain RH, the knockout mice displayed decreased resistance consistent with absence of CD4+ effectors. Nevertheless, these animals generated CD8+ lymphocyte effectors capable of mediating partial protection through IFN-gamma secretion. Moreover, in vivo neutralization experiments indicated that the development of resistance in knockout mice depends on CD4+ cells as well as interleukin 2 (IL-2). The identity of the IL-2-producing protective cell population was further characterized as CD4+, NK1.1+ by in vitro depletion studies and reverse transcriptase-PCR analysis of fluorescence-activated cell sorter (FACS)-purified CD4+ NK1.1+ T lymphocytes. These results demonstrate that in the absence of conventional MHC class II-restricted CD4+ T lymphocytes, CD8 priming persists and mediates partial protective immunity to T. gondii. Moreover, the data argue that CD4+, NK1.1+ cells, previously implicated in the initiation of T helper cell 2 (Th2) responses through their production of IL-4, can also play a role as alternative IL-2-secreting helper cells in Th1-mediated host resistance to infection.
Denkers
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EY
Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Scharton-Kersten
T
T
Barbieri
S
S
Caspar
P
P
Sher
A
A
D000818:Animals; D000941:Antigens / Q000276:immunology; D000950:Antigens, Ly; D000953:Antigens, Protozoan / Q000276:immunology; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008211:Lymphocyte Cooperation; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology*
D000941:Antigens; D000950:Antigens, Ly; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D007371:Interferon-gamma