AIDS patients less than a year of age are more likely to be diagnosed with and have a more fulminate course of Pneukocystis carinii pneumonia (PCP) than older children. This may be due to the immaturity of the acquired immune system. We have reported that there is a 3 week delay in the acquired immune response of mice give P. carinii (PC) as newborns compared to those infected as adults [Garvy, 1996]. This delay may be due to 1) inefficient recognition, phagocytosis, and/or antigen presentation by lung macrophages or dendritic cells; or 2) inefficient lymphocytic responses possibly due to immaturity or function of low frequency of specific cells. The goal of this proposal is to test the hypothesis that delayed clearance of PC from the lungs of newborn mice is due to inadequate immune responses reflecting immaturity of the acquired immune system, including defective antigen recognition and processing, and/or lung lymphocyte responses. Two basic immunological questions are addressed by the specific aims: 1) is the postnatal lung competent to recognize foreign antigens, process them, and present them to lymphocytes and 2) are lymphocytes from neonates competent to respond to presented antigen resulting in resolution of PCP? The specific aims to be addressed are 1) determine whether the neonatal lung is capable of recognizing and processing antigen leading to an efficient specific immune response; 2) determine whether the immaturity of neonatal B cells results in delayed clearance of PC from the lungs of newborn mice; and 4) determine whether aerosols of heat-killed E. coli or anti-CD40 to cause an inflammatory response will either a) increase exposure of PC to maternal antibody or b) stimulate either specific or non-specific immune responses to PC. Adoptive transfer models of adult lymphocytes into newborns or neonatal lymphocytes into PC-infected adult SCID, CD4/- -, or B cell-deficient mice will be used extensive to address the specific aims. Additionally, ex vivo and in vitro assays will be used to examine the functional capacity or lung lymphocytes in newborn mice. The studies proposed will provide new insight into the host defense in the lungs of neonates.
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