Cytokine profiles of bronchoalveolar lavage cells from mice with influenza pneumonia: consequences of CD4+ and CD8+ T cell depletion.
Cytokine production and mRNA profiles have been analyzed at the single cell level for bronchoalveolar lavage (BAL) populations from mice infected with an influenza A virus in the presence or absence of the CD4+ and CD8+ T cell subsets. Phagocytes were identified by their capacity to engulf latex particles, but the cellular elements of this inflammatory process were otherwise not characterized. BAL preparations from undepleted mice contained numerous IL-2, IL-4 and IFN-gamma-producing cells, with many fewer secreting TNF or IL-10. The frequency of mRNA+ cells detected by in situ hybridization was, in general, much higher than that for protein-secreting cells determined by ELISPOT analysis. In addition to IL-2, IL-4, and IFN-gamma, large numbers of cells were found to contain IL-10 and TNF-beta transcripts. Depletion of CD4+ and CD8+ cells caused significant reduction in the frequency of IL-2 and IL-4-producing cells, but even simultaneous elimination of both T cell subsets failed to totally remove all cells producing these cytokines. Similarly, a residual population of IFN-gamma-producing cells remained after depletion of the CD4+ and CD8+ subsets. Likely sources of these cytokines (apart from NK cells) are the CD4-8- alpha beta and gamma delta T cells found previously in BAL populations from doubly-depleted mice infected with this virus. Somewhat surprisingly, mRNA for IFN-gamma, IL-5, and TNF beta was prevalent in cells that had engulfed latex particles, though mRNA for IL-2 and IL-4 was never detected in macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Sarawar
S R
SR
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Carding
S R
SR
Allan
W
W
McMickle
A
A
Fujihashi
K
K
Kiyono
H
H
McGhee
J R
JR
Doherty
P C
PC
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D008212:Lymphocyte Depletion; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology; D011024:Pneumonia, Viral / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016827:CD8 Antigens; D016207:Cytokines; D012333:RNA, Messenger