The relative importance of CD4+ and CD8+T cells in immunity to pulmonary paracoccidioidomycosis.
Protective immunity in paracoccidioidomycosis (PCM) is believed to be mediated by cellular immunity, but the role of T cell subsets has never been investigated. The aim of this study was to characterize the function of CD4+ and CD8+ T cells in the immunity developed by susceptible, intermediate and resistant mice after P. brasiliensis infection. In susceptible mice, depletion of CD4+ T cells did not alter disease severity and anergy of cellular immunity but diminished antibody production. Anti-CD8 treatment led to increased fungal loads, but restored DTH reactivity. In resistant mice, both CD4+ and CD8+ T cells control fungal burdens and cytokines although only the former regulate DTH reactions and antibody production. In the intermediate strain, deficiency of whole T and CD8+ T cells but not of CD4+ T or B cells led to increased mortality rates. Thus, in pulmonary PCM: (a) irrespective of the host susceptibility pattern, fungal loads are mainly controlled by CD8+ T cells, whereas antibody production and DTH reactions are regulated by CD4+ T cells; (c) CD4+ T cells play a protective role in the resistant and intermediate mouse strains, whereas in susceptible mice they are deleted or anergic; (d) genetic resistance to PCM is associated with concomitant CD4+ and CD8+ T cell immunity secreting type 1 and type 2 cytokines.
Chiarella
Andressa P
AP
Departamento de Imunologia do Instituto de Ciências Biomédicas da Universidade de São Paulo, Av. Prof. Lineu Prestes 1730, CEP 05508-900, São Paulo, Brazil.
Arruda
Celina
C
Pina
Adriana
A
Costa
Tânia A
TA
Ferreira
Rita C V
RC
Calich
Vera L G
VL
D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000382:microbiology; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D010228:Paracoccidioides / Q000276:immunology; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000382:microbiology; D013154:Spleen / Q000276:immunology / Q000382:microbiology
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007378:Interleukins